Skip to content
2000
Volume 23, Issue 1
  • ISSN: 1570-1611
  • E-ISSN: 1875-6212

Abstract

Mendelian Randomization (MR) studies have emerged as a powerful tool for investigating causal relationships between modifiable risk factors and clinical outcomes, using genetic variants as instrumental variables. In the context of vitamin D research, MR is a promising approach to elucidate the effects of vitamin D on various health outcomes, including adverse cardiovascular events. However, the validity of MR analyses relies heavily on the strength of the genetic associations found. “Weak instrument bias”, arising from instruments with low explanatory power for the exposure of interest, can lead to biased estimates and compromise causal inference. We have, herein, briefly reviewed the challenges posed by weak instrument bias in a large MR study on vitamin D [25(OH)D] and stroke, exploring implications for the study's validity and reliability of findings. We have then added an original meta-analysis stratified by 25(OH)D levels. By using aggregated data from a recent MR study, an original meta-analysis stratified by population mean levels of 25(OH)D has indicated that interventions based on vitamin D supplementations in population mean levels ranging from 50 to 70 nmol/L are likely to translate into a 13% reduction of stroke risk (pooled odds ratio=0.873, 95% CI: 0.764-0.997, p-value=0.04). MR studies are a valuable approach for discerning causal relationships between exposures, such as vitamin D, and health outcomes. However, the effectiveness of MR analyses depends on the robustness of the genetic instruments employed. By recognizing and addressing weak instrument bias in MR studies of vitamin D, researchers can enhance the credibility and utility of causal inference in understanding the health effects of this essential nutrient. A meta-analysis stratified by population mean levels of 25(OH)D has revealed the potential benefits of targeted interventions with vitamin D supplementations for stroke.

Loading

Article metrics loading...

/content/journals/cvp/10.2174/0115701611331890241007112502
2024-10-08
2025-04-12
Loading full text...

Full text loading...

References

  1. BoefA.G.C. DekkersO.M. le CessieS. Mendelian randomization studies: A review of the approaches used and the quality of reporting.Int. J. Epidemiol.201544249651110.1093/ije/dyv071 25953784
    [Google Scholar]
  2. SofianopoulouE. KaptogeS.K. AfzalS. Estimating dose-response relationships for vitamin D with coronary heart disease, stroke, and all-cause mortality: Observational and Mendelian randomisation analyses.Lancet Diabetes Endocrinol.2024121e2e1110.1016/S2213‑8587(23)00287‑5 38048800
    [Google Scholar]
  3. BennM. NordestgaardB.G. From genome-wide association studies to Mendelian randomization: Novel opportunities for understanding cardiovascular disease causality, pathogenesis, prevention, and treatment.Cardiovasc. Res.201811491192120810.1093/cvr/cvy045 29471399
    [Google Scholar]
  4. CosciaC. GillD. BenítezR. PérezT. MalatsN. BurgessS. Avoiding collider bias in Mendelian randomization when performing stratified analyses.Eur. J. Epidemiol.202237767168210.1007/s10654‑022‑00879‑0 35639294
    [Google Scholar]
  5. CuiA. ZhangT. XiaoP. FanZ. WangH. ZhuangY. Global and regional prevalence of vitamin D deficiency in population-based studies from 2000 to 2022: A pooled analysis of 7.9 million participants.Front. Nutr.202310107080810.3389/fnut.2023.1070808 37006940
    [Google Scholar]
  6. ZhouR. WangM. HuangH. LiW. HuY. WuT. Lower vitamin D status is associated with an increased risk of ischemic stroke: A systematic review and meta-analysis.Nutrients201810327710.3390/nu10030277 29495586
    [Google Scholar]
  7. LeongA. RehmanW. DastaniZ. The causal effect of vitamin D binding protein (DBP) levels on calcemic and cardiometabolic diseases: A Mendelian randomization study.PLoS Med.20141110e100175110.1371/journal.pmed.1001751 25350643
    [Google Scholar]
  8. ChanY.H. SchoolingC.M. ZhaoJ. Mendelian randomization focused analysis of vitamin D on the secondary prevention of ischemic stroke.Stroke202152123926393710.1161/STROKEAHA.120.032634 34565175
    [Google Scholar]
  9. VimaleswaranK.S. CavadinoA. BerryD.J. Association of vitamin D status with arterial blood pressure and hypertension risk: A mendelian randomisation study.Lancet Diabetes Endocrinol.20142971972910.1016/S2213‑8587(14)70113‑5 24974252
    [Google Scholar]
  10. HsiaJ. HeissG. RenH. Calcium/vitamin D supplementation and cardiovascular events.Circulation2007115784685410.1161/CIRCULATIONAHA.106.673491 17309935
    [Google Scholar]
  11. ScraggR. StewartA.W. WaayerD. Effect of monthly high-dose vitamin D supplementation on cardiovascular disease in the Vitamin D Assessment Study: A randomized clinical trial.JAMA Cardiol.20172660861610.1001/jamacardio.2017.0175 28384800
    [Google Scholar]
  12. FordJ.A. MacLennanG.S. AvenellA. BollandM. GreyA. WithamM. Cardiovascular disease and vitamin D supplementation: Trial analysis, systematic review, and meta-analysis.Am. J. Clin. Nutr.2014100374675510.3945/ajcn.113.082602 25057156
    [Google Scholar]
/content/journals/cvp/10.2174/0115701611331890241007112502
Loading
/content/journals/cvp/10.2174/0115701611331890241007112502
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test